Investigating chiral morphogenesis of gold using generative cellular automata.

Homochirality is an important feature in biological systems and occurs even in inorganic nanoparticles. However, the mechanism of chirality formation and the key steps during growth are not fully understood. Here we identify two distinguishable pathways from achiral to chiral morphologies in gold nanoparticles by training an artificial neural network of cellular automata according to experimental results. We find that the chirality is initially determined by the nature of the asymmetric growth along the boundaries of enantiomeric high-index planes. The deep learning-based interpretation of chiral morphogenesis provides a theoretical understanding but also allows us to predict an unprecedented crossover pathway and the resulting morphology.

Morc2a variants cause hydroxyl radical-mediated neuropathy and are rescued by restoring GHKL ATPase.

Mutations in the Microrchidia CW-type zinc finger 2 (MORC2) GHKL ATPase module cause a broad range of neuropathies, such as Charcot-Marie-Tooth disease type 2Z; however, the aetiology and therapeutic strategy are not fully understood. Previously, we reported that the Morc2a p.S87L mouse model exhibited neuropathy and muscular dysfunction through DNA damage accumulation. In the present study, we analysed the gene expression of Morc2a p.S87L mice and designated the primary causing factor. We investigated the pathological pathway using Morc2a p.S87L mouse embryonic fibroblasts and human fibroblasts harbouring MORC2 p.R252W. We subsequently assessed the therapeutic effect of gene therapy administered to Morc2a p.S87L mice. This study revealed that Morc2a p.S87L causes a protein synthesis defect, resulting in the loss of function of Morc2a and high cellular apoptosis induced by high hydroxyl radical levels. We considered the Morc2a GHKL ATPase domain as a therapeutic target because it simultaneously complements hydroxyl radical scavenging and ATPase activity. We used the adeno-associated virus (AAV)-PHP.eB serotype, which has a high CNS transduction efficiency, to express Morc2a or Morc2a GHKL ATPase domain protein in vivo. Notably, AAV gene therapy ameliorated neuropathy and muscular dysfunction with a single treatment. Loss-of-function characteristics due to protein synthesis defects in Morc2a p.S87L were also noted in human MORC2 p.S87L or p.R252W variants, indicating the correlation between mouse and human pathogenesis. In summary, CMT2Z is known as an incurable genetic disorder, but the present study demonstrated its mechanisms and treatments based on established animal models. This study demonstrates that the Morc2a p.S87L variant causes hydroxyl radical-mediated neuropathy, which can be rescued through AAV-based gene therapy.

Polyphenol-Enabled 2D Nanopatch for Enhanced Nasal Mucoadhesion and Immune Activation.

The advancement of effective nasal mucoadhesive delivery faces challenges due to rapid mucociliary clearance (MCC). Conventional studies have employed mucoadhesive materials, mainly forming spherical nanoparticles, but these offer limited adhesion to the nasal mucosa. This study hypothesizes that a 2D nanoscale structure utilizing adhesive polyphenols can provide a superior strategy for countering MCC, aligning with the planar mucosal layers. We explore the use of tannic acid (TA), a polyphenolic molecule known for its adhesive properties and ability to form complexes with biomolecules. Our study introduces an unprecedented 2D nanopatch, assembled through the interaction of TA with green fluorescent protein (GFP), and cell-penetrating peptide (CPP). This 2D nanopatch demonstrates robust adhesion to nasal mucosa and significantly enhances immunoglobulin A secretions, suggesting its potential for enhancing nasal vaccine delivery. The promise of a polyphenol-enabled adhesive 2D nanopatch signifies a pivotal shift from conventional spherical nanoparticles, opening new pathways for delivery strategies through respiratory mucoadhesion.

High-Efficiency Interdigitated Electrode-Based Droplet Merger for Enabling Error-Free Droplet Microfluidic Systems.

Merging two droplets into a droplet to add and mix two contents is one of the common droplet microfluidic functions with droplet generation and sorting, performing broad ranges of biological and chemical assays in droplets. However, traditional droplet-merging techniques often encounter unsynchronized droplets, causing overmerging or mis-merging, and unwanted merging outside of the desired zone. This is more severe when the incoming droplets to be merged are polydisperse in their sizes, often observed in assays that require long-term incubation, elevated-temperature, and/or multiple droplet processing steps. Here, we developed an interdigitated electrode (IDE)-based droplet merger consisting of a droplet autosynchronizing channel and a merging channel. The autosynchronizing channel provides >95% merging efficiency even when 20% polydispersity in the droplet size exists. The highly localized and enhanced dielectrophoretic force generated by the IDEs on the channel bottom allows droplet merging at an extremely low voltage (4.5 V) and only locally at the IDE region. A systematic evaluation of how various design and operation parameters of the IDE merger, such as IDE finger dimensions, dielectric coating layer thickness, droplet size, and droplet flow speed impact the performance was conducted. The optimized device showed consistent performance even when operating for up to 100 h consecutively at high throughput (100 droplets/s). The presented technology has been integrated into a droplet microfluidics workflow to test the lytic activities of bacteriophage on bacterial host cells with 100% merging efficiency. We expect this function to be integrated into droplet microfluidic systems performing broad ranges of high-throughput chemical and biological assays.

Atomically Dispersed Ru-doped Ti4O7 Electrocatalysts for Chlorine Evolution Reaction with a Universal Activity.

Chlorine has been supplied by the chlor-alkali process that deploys dimensionally stable anodes (DSAs) for the electrochemical chlorine evolution reaction (ClER). The paramount bottlenecks have been ascribed to an intensive usage of precious elements and inevitable competition with the oxygen evolution reaction. Herein, a unique case of Ru2+-O4 active motifs anchored on Magnéli Ti4O7 (Ru-Ti4O7) via a straightforward wet impregnation and mild annealing is reported. The Ru-Ti4O7 performs radically active ClER with minimal deployment of Ru (0.13 wt%), both in 5 m NaCl (pH 2.3) and 0.1 m NaCl (pH 6.5) electrolytes. Scanning electrochemical microscopy demonstrates superior ClER selectivity on Ru-Ti4O7 compared to the DSA. Operando X-ray absorption spectroscopy and density functional theory calculations reveal a universally active ClER (over a wide range of pH and [Cl-]), through a direct adsorption of Cl- on Ru2+-O4 sites as the most plausible pathway, together with stabilized ClO* at low [Cl-] and high pH.

Atomistic Scale Modeling of Anode/Electrolyte Interfaces in Li-Ion Batteries.

A key issue in lithium-ion batteries is understanding the solid electrolyte interphase (SEI) resulting from a reductive reaction on the anode/electrolyte interface. The presence of the SEI layer affects the transport behavior of the ions and electrons between the anode and electrolyte. Despite the influence on interfacial properties, the formation and evolution mechanism of the SEI layer are unclear owing to their complexity and dynamic nature. Atomistic-scale simulations have promoted the understanding of the reaction mechanism on the anode/electrolyte interface, the formation and evolution of the SEI layer, and their fundamental properties. This Perspective discusses the modeling and interpretations of anode/SEI/electrolyte interfaces through computational methods at the atomic-scale and highlights interfacial modeling techniques for a realistic interface design, which can overcome the limited time and length scale with high accuracy.

Circular polarization sensitive opto-neuromorphic operation at plasmonic hot electron transistor using chiral gold nanoparticles.

Opto-neuromorphic operation is critical for biological system to recognize the visual objects and mimicking such operation is important for artificial prosthesis as well as machine vision system for industrial applications. To sophisticatedly mimic biological system, regulation of learning and memorizing efficiency is needed, however engineered synthetic platform has been lack of controllability, which makes huge gap between biological system and synthetic platform. Here we demonstrated controllable learning and memorizing opto-neuromorphic operation at plasmonic hot electron transistor. Especially, circularly polarized light (CPL) sensitive synaptic characteristics and learning experience capability are enabled by incorporating chiral plasmonic nanoparticle. Furthermore, gate voltage gives rise to controllable neuromorphic operation due to hot electron injection and trapping effect, resulting in high remaining synaptic weight of ∼70% at negative gate voltage under CPL excitation. We believe that this discovery makes significant leap toward on-demand in-sensor computing as well as toward bio-realistic device.

Chiral plasmonic sensing: From the perspective of light-matter interaction.

Molecular chirality is represented as broken mirror symmetry in the structural orientation of constituent atoms and plays a pivotal role at every scale of nature. Since the discovery of the chiroptic property of chiral molecules, the characterization of molecular chirality is important in the fields of biology, physics, and chemistry. Over the centuries, the field of optical chiral sensing was based on chiral light-matter interactions between chiral molecules and polarized light. Starting from simple optics-based sensing, the utilization of plasmonic materials that could control local chiral light-matter interactions by squeezing light into molecules successfully facilitated chiral sensing into noninvasive, ultrasensitive, and accurate detection. In this Review, the importance of plasmonic materials and their engineering in chiral sensing are discussed based on the principle of chiral light-matter interactions and the theory of optical chirality and chiral perturbation; thus, this Review can serve as a milestone for the proper design and utilization of plasmonic nanostructures for improved chiral sensing.

Development and evaluation of extracorporeal membrane oxygenation nursing education program for nursing students using virtual reality.

BACKGROUND: This study aims to improve nursing students' ability to care for critically ill patients through education in extracorporeal membrane oxygenation (ECMO) nursing. METHODS: This study developed a virtual reality (VR) simulation program for the five-step ECMO nursing of the Analysis, Design, Development, Implement, and Evaluation (ADDIE) model and used an equivalent control group pre-test and post-test no-synchronized design to verify the effect. The participants of this study were fourth-year nursing students enrolled in nursing departments at three universities in Seoul, Gangwon, and Gyeonggi in South Korea; it included 66 participants, 33 in each of the experimental and control groups. The program consisted of pre-training, orientation, VR simulation, and debriefing. RESULTS: The interaction effect of the intervention and control groups with time points using the ECMO nursing VR simulation program was rejected due to no statistically significant difference in knowledge (F = 1.41, p = .251), confidence (F = 1.97, p = .144), and clinical reasoning capacity (F = 2.85, p = .061). However, learning immersion (t = 3.97, p < .001) and learning satisfaction (t = 4.25, p < .001) were statistically significantly higher in the experimental group than in the control group. CONCLUSION: VR simulation program for ECMO nursing developed in this study is a potential educational method that positively affects the learning immersion and learning satisfaction of nursing students.

Maxillary Sinus Augmentation and Implant Installation in Patients With Pseudocysts and Mucous Retention Cysts.

This case study systematically assessed diverse approaches to sinus augmentation in the presence of sinus pathology. Three patients were carefully selected and categorized as pseudocyst (PsC) (type 1), mucous retention cyst (MRC) smaller than 20 mm (type 2), and MRC larger than 20 mm in size (type 3). All patients underwent sinus augmentation procedures, with each case utilizing a unique surgical approach. Spontaneous drainage was performed for the patient with PsC (type 1), followed by uncomplicated sinus augmentation. For the patient with an MRC smaller than 20 mm (type 2), aspiration of the cyst contents preceded sinus augmentation. Conversely, the patient with a larger MRC (type 3) underwent cyst enucleation followed by sinus augmentation after complete recovery of the sinus membrane. No complications were noted in any of the cases, and follow-up revealed stable implant installation at the site of sinus augmentation. Within the constraints of this study, the choice of surgical procedure, whether involving spontaneous drainage, aspiration, or enucleation, should be guided by an anticipated pathologic diagnosis and the size of the sinus cyst. This informed approach empowers clinicians to make well-informed decisions for the best possible outcomes and sustained results. Overall, this study offers valuable insights for clinicians seeking to optimize sinus augmentation procedures in the presence of sinus pathology.

Three-Dimensional Analysis of Bone Remodeling After Closed Treatment for Mandibular Condylar Head Fracture.

Closed treatment of mandibular condylar fractures has been used for its indications based on the fracture site, fracture status, and patient age. Posttreatment mandibular condyle size is associated with mandibular function; however, a few studies have reported bone remodeling patterns and volume changes in the condyle and glenoid fossa after mandibular condylar head fractures (CHFs). Therefore, volumetric changes in the mandibular condyle and glenoid fossa were analyzed in the present study, and bone remodeling patterns were evaluated after mandibular CHFs. The present study included 16 condyles from 12 patients who received closed treatment for CHF. After reconstruction of a 3-dimensional skull model, including the mandible, using computed tomography data taken immediately after injury and 6 months after treatment, volume changes in the mandibular condyle and glenoid fossa were analyzed. The condylar volume increased by 0.32±0.66 cm3 during the 6-month healing period without statistical significance (P=0.093). Regarding the glenoid fossa, the fossa showed a statistically significant volume increase of 0.41±0.59 cm3 (P=0.021), and 12 glenoid fossae (75%) showed downward bone apposition; however, no change or only mild bone resorption was observed in 4 glenoid fossae (25%). The results of this study indicated that the volume changes in the mandibular condyle after closed treatment of a mandibular CHF are not significant, and the glenoid fossa adapts to the displaced mandibular condyle through downward growth accompanied by volume increase.

Retinal Neurodegeneration in an Intraocular Pressure Fluctuation Rat Model.

Increased intraocular pressure (IOP) is the most important risk factor for glaucoma. The role of IOP fluctuation, independently from elevated IOP, has not yet been confirmed in glaucoma. We investigated the effects of IOP fluctuation itself on retinal neurodegeneration. Male rats were treated with IOP-lowering eyedrops (brinzolamide and latanoprost) on Mondays and Thursdays (in the irregular instillation group) or daily (in the regular instillation group), and saline was administered daily in the normal control group for 8 weeks. The IOP standard deviation was higher in the irregular instillation group than the regular instillation group or the control group. The degree of oxidative stress, which was analyzed by labeling superoxide, oxidative DNA damage, and nitrotyrosine, was increased in the irregular instillation group. Macroglial activation, expressed by glial fibrillary acidic protein in the optic nerve head and retina, was observed with the irregular instillation of IOP-lowering eyedrops. Microglial activation, as indicated by Iba-1, and the expression of TNF-α did not show a significant difference between the irregular instillation and control groups. Expression of cleaved caspase-3 was upregulated and the number of retinal ganglion cells (RGCs) was decreased in the irregular instillation group. Our findings indicate that IOP fluctuations could be induced by irregular instillation of IOP-lowering eyedrops and this could lead to the degeneration of RGCs, probably through increased oxidative stress and macrogliosis.

In vivo LNP-CRISPR Approaches for the Treatment of Hemophilia.

Hemophilia is a genetic disorder that is caused by mutations in coagulation factor VIII (hemophilia A) or IX (hemophilia B) genes resulting in blood clotting disorders. Despite advances in therapies, such as recombinant proteins and products with extended half-lives, the treatment of hemophilia still faces two major limitations: the short duration of therapeutic effect and production of neutralizing antibodies against clotting factors (inhibitor). To overcome these limitations, new hemophilia treatment strategies have been established such as gene therapy, bispecific antibody, and rebalancing therapy. Although these strategies have shown promising results, it is difficult to achieve a permanent therapeutic effect. Advances in the clustered regularly interspaced short palindromic repeat (CRISPR) technology have allowed sustainable treatment by correcting mutated genes. Since genome editing generates irreversible changes in host genome, safety must be ensured by delivering target organs. Therefore, the delivery tool of the CRISPR system is crucial for safe, accurate, and efficient genome editing. Recently, non-viral vector lipid nanoparticles (LNPs) have emerged as safer tools for delivering CRISPR systems than other viral vectors. Several previous hemophilia pre-clinical studies using LNP-CRISPR showed that sufficient and sustainable therapeutic effects, which means that LNP-CRISPR-mediated genome-editing therapy can be a valid option for the treatment of hemophilia. In this paper, we summarize the latest advancements in the successful treatment of hemophilia and the potential of CRISPR-mediated genome-editing therapy using LNPs.

Serial Dual Mediating Effects of Parenting Stress on Life Satisfaction among Parents of School-Aged Children with Chronic Conditions.

This study examines the serial dual mediating effects of marital conflict and self-esteem on the relationship between parenting stress and life satisfaction in parents of school-aged children with chronic conditions. This study aims to present foundational data for developing nursing interventions for parents caring for children with chronic illnesses. Of the 2150 parents who participated in the 13th Panel Study on Korean Children (PSKC), 271 raising a child with a chronic illness were enrolled in the study. The serial dual mediating effect was analyzed using PROCESS macro Model 6. The serial dual mediating effects of parenting stress, marital conflict, and self-esteem on parents' life satisfaction were analyzed. Marital conflict and self-esteem had significant serial multiple mediating effects on the relationship between stress and life satisfaction in fathers (B = -0.11, bootstrap 95% CI = -0.16--0.06) and mothers (B = -0.06, bootstrap 95% CI = -0.09--0.03). Our results suggest that marital conflict increases with increasing parenting stress and that increased marital conflict sequentially reduces self-esteem, ultimately diminishing life satisfaction in parents raising a child with a chronic condition. Thus, relevant nursing interventions and social support are essential to boost the life satisfaction of parents raising children with chronic conditions.

An Exploratory Analysis of the Roles of Nurses on a Pediatric Rehabilitation Unit in South Korea Perceived by Pediatric Rehabilitation Professionals.

Rehabilitation addresses not only children's disabilities but also their physical, psychological, social, and cultural impairments. Hence, pediatric rehabilitation adopts a multidisciplinary approach; it encompasses the vital role of not only physicians and rehabilitation therapists, but also of nurses. This study conducts a content analysis of the experiences of healthcare professionals specializing in pediatric rehabilitation to explore the roles nurses working on pediatric rehabilitation units are expected to perform. After analyzing the interviews with 12 experts in pediatric rehabilitation, the roles of pediatric rehabilitation nurses were broadly categorized into five areas (caregivers, team members, counselors, researchers, and educators) with eight sub-groups and 24 specific roles. This study is significant because it provides profound insights into the roles of pediatric rehabilitation nurses in Korea. These insights can serve as foundational data for formulating policies for healthcare personnel in pediatric rehabilitation, and provide evidence for establishing a much-needed system for certified rehabilitation nurses in Korea.

Safety evaluation of vitamin K2 (menaquinone-7) via toxicological tests.

This study aims to evaluate the safety of MK-7 produced by fermentation process using a Bacillus subtilis var. natto strain for human ingestion via acute oral toxicity, repeated dose 90-day oral toxicity, 28-day recovery test, and genotoxicity tests. The acute oral toxicity test results indicated that all subjects survived at the dose of 5000 mg/kg with no toxic effects. For the repeated dose 90-day oral toxicity test, MK-7 was administered to rats at 500, 1500, and 4500 mg/kg for 90 d. No abnormal findings were detected in clinical observations or in clinical pathological and histopathological examinations. The no-observed-adverse-effect level(NOAEL) was determined to be 4500 mg/kg/d, the maximum dose tested. For the evaluation of genotoxicity, reverse mutation, chromosomal aberration, and micronucleus tests were performed. In the reversion mutation test, vitamin K2 did not induce reversion in bacterial strains, and no chromosomal abnormality was observed in the chromosomal abnormality test using Chinese hamster lung cells. In the micronucleus test, micronuclei were not induced using ICR mouse bone marrow cells. All the toxicity test results suggest that vitamin K2 produced by fermentation processes using Bacillus subtilis var. natto induced no toxicological changes under the experimental conditions.

Accelerated Structural Optimization for the Supported Metal System Based on Hybrid Approach Combining Bayesian Optimization with Local Search.

Numerous systematic methods have been developed to search for the global minimum of the potential energy surface, which corresponds to the optimal atomic structure. However, the majority of them still demand a substantial computing load due to the relaxation process that is embedded as an inner step inside the algorithm. Here, we propose a hybrid approach that combines Bayesian optimization (BO) and a local search that circumvents the relaxation step and efficiently finds the optimum structure, particularly in supported metal systems. The hybridization strategy combining the capabilities of BO's effective exploration and the local search's fast convergence expedites structural search. In addition, the formulation of physical constraints regarding the materials system and the feature of screening structure similarity enhance the computational efficiency of the proposed method. The proposed algorithm is demonstrated in two supported metal systems, showing the potential of the proposed method in the field of structural optimization.

Impact of Long-Term Supplementation with Probiotics on Gut Microbiota and Growth Performance in Post-Weaned Piglets.

This study aimed to investigate effects of long-term probiotic supplementation on gut microbiota and growth performance in health weaned piglets. The non-probiotic group (N-PrB) was fed only a basal diet, while the probiotic group (PrB) was fed a basal diet + probiotic combination (E. faecium 1.6 × 108 CFU/g, B. subtilis 2.0 × 108 CFU/g, S. cerevisiae 3.0 × 108 CFU/g). The probiotics combination was provided to the PrB, mixing with the basal diet in 5 kg/ton. As a result, the PrB exhibited significantly improved weight gain compared to the N-PrB (p = 0.00991). In the gut microbiome analysis, the PrB exhibited a significant increasing tendency of α-diversity compared to those of the N-PrB (p < 0.01). In the bacterial relative abundance changes in bacteria comprising the gut microbiota, Ruminococcaceae (p = 0.00281) and Prevotella (p = 0.00687) tended to significantly increase in the PrB, but decreased in the N-PrB. The Eubaterium coprostanoligenes group exhibited an increasing tendency in both groups, but tended to increase more significantly in the PrB compared to the N-PrB (p = 0.00681). Muribaculaceae tended to significantly increase in the N-PrB, but decreased in the PrB (p = 0.002779). In this study, significant differences on the gut microbiome were found according to the probiotics supplementation in the weaned piglets and these gut microbiome changes appeared to improve the growth performance.

Exploring Neuroprotective Effects of Topical Brimonidine in Experimental Diabetic Retinopathy.

BACKGROUND/AIM: Diabetic retinopathy is a leading cause of blindness worldwide, characterized by neurovascular dysfunction. This study aimed to investigate the impact of brimonidine, a selective adrenoceptor agonist, on diabetic retinal neurodegeneration, recognizing the critical role of neurodegeneration in diabetic retinopathy. MATERIALS AND METHODS: Streptozotocin-induced diabetes was established in adult male Sprague-Dawley rats to mimic diabetic retinopathy. Rats, except non-diabetic control rats, received topical applications of 0.15% brimonidine tartrate (treatment group) or balanced salt solution (diabetic control group) twice daily following diabetes induction. Each group comprised six randomly assigned animals. Retinal samples were analyzed using immunofluorescence staining, apoptosis assay, and western blot. RESULTS: Topical brimonidine treatment reduced apoptosis of retinal ganglion cells at 8 weeks after induction of diabetes (p<0.05). Glial activation induced by diabetes was reduced by brimonidine treatment. Immunoblot and immunofluorescence assay revealed that the decrease in phospho- protein kinase B (AKT) level resulting from diabetes was also attenuated by brimonidine (p<0.05). Furthermore, brimonidine alleviated the decrease in anti-apoptotic proteins [BCL2 apoptosis regulator (BCL2) and BCL-xl] induced by diabetes (p<0.05). Elevation of phospho-p38 mitogen-activated protein kinase (p38MAPK) and p53 in diabetic rats were reduced by brimonidine (p<0.05). Additionally, brimonidine treatment attenuated the upregulation of the pro-apoptotic molecule BCL-2 associated X in retinas of diabetic rats (p<0.05). CONCLUSION: These findings suggest that topical brimonidine treatment may protect retinal ganglion cells in experimental diabetes by modulating the AKT pathway and reducing pro-apoptotic p38MAPK levels. This presents a potential neuroprotective approach in diabetes, offering the advantage of localized treatment without the added burden of oral medication.

Multislice computed tomography demonstrating mental nerve paresthesia caused by periapical infection: A case report.

Components derived from an infected lesion within the bone can spread through various passages in the mandible, particularly via the mental foramen. Radiologically, the spread of infection is typically nonspecific and challenging to characterize; however, multislice computed tomography (MSCT) can effectively detect pathological changes in soft tissues and the bone marrow space. This report describes the case of a 55-year-old woman who experienced mental nerve paresthesia due to a periapical infection of the right mandibular second premolar. MSCT imaging revealed increased attenuation around the periapical lesion extending into the mandibular canal and loss of the juxtamental foraminal fat pad. Following endodontic treatment of the tooth suspected to be the source of the infection, the patient's symptoms resolved, and the previous MSCT imaging findings were no longer present. Increased bone marrow attenuation and obliteration of the fat plane in the buccal aspect of the mental foramen may serve as radiologic indicators of inflammation spreading from the bone marrow space.